title: Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study.
abstract: BACKGROUND
  Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients.
  
  
  METHODS
  We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 ± 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR).
  
  
  RESULTS
  CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 ± 0.81 vs 0.76 ± 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 ± 0.84 vs 1.35 ± 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves.
  
  
  CONCLUSIONS
  We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.
authors.affiliation: Department of Cardiology, University Hospital of the RWTH, Pauwelsstraße 30, D- 52057 Aachen, Germany. Vincent.Brandenburg@post.rwth-aachen.de.
authors.forename: Vincent M
authors.initials: VM
authors.lastname: Brandenburg
authors.forename: Rafael
authors.initials: R
authors.lastname: Kramann
authors.forename: Ralf
authors.initials: R
authors.lastname: Koos
authors.forename: Thilo
authors.initials: T
authors.lastname: Krüger
authors.forename: Leon
authors.initials: L
authors.lastname: Schurgers
authors.forename: Georg
authors.initials: G
authors.lastname: Mühlenbruch
authors.forename: Sinah
authors.initials: S
authors.lastname: Hübner
authors.forename: Ulrich
authors.initials: U
authors.lastname: Gladziwa
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002114:Calcinosis / Q000097:blood* / Q000209:etiology; D003324:Coronary Artery Disease / Q000097:blood* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005819:Genetic Markers; D006330:Heart Defects, Congenital / Q000097:blood* / Q000209:etiology; D006349:Heart Valve Diseases / Q000097:blood* / Q000209:etiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000534:rehabilitation*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human